The proposed research, which was stimulated by the finding of decreased glutathione (GSH) levels in peripheral blood mononuclear cells and plasma of patients who are seropositive for HIV infection, and by independent studies which indicate that glutathione is required for T-lymphocyte proliferation, have the following specific aims: (I) To elucidate the properties of GSH that are involved in cellular proliferation and that may be involved in virus production, (II) To examine the synthesis and utilization of GSH by normal and HIV-infected cells, and (III) To study the effects of modulation of cellular GSH on the toxicity of certain drugs used in therapy of AIDS. These investigations are expected to form a necessary background of information required for possible therapy of HIV-infection by using approaches that increase cellular levels of GSH. Such therapy may consist of administration of (a) cysteine precursors, (b) gamma-glutamylcysteine or its precursors, (c) glutathione, or (d) glutathione derivatives such as glutathione monoesters. Approaches (a), (b) , and (c) require that the cellular catalysts necessary for GSH synthesis (gamma-glutamylcysteine synthetase and glutathione synthetase) are functional and that cellular energy is available. Approach (c) also requires the activity of gamma-glutamyl transpeptidase. On the other hand, approach (d) in which GSH mono esters are applied does not require cellular energy or the enzymes involved in GSH metabolism.